A team of immunologists at the University of Massachusetts Amherst has turned what we know about T-cells, one of the most important parts of the body’s immune system, on its head, opening the door to next-generation cancer vaccines.
The research, published recently in Science Advances, describes a novel and unusual mechanism for T-cells to remember the pathogens and cancers that they had previously encountered. This immunological memory is crucial to the body’s immune response and is the basis of how vaccines work, and boosting cellular memory to recognize tumors could help improve cancer therapies.
Our bodies have different types of T-cells, which are white blood cells. One type is CD8 T cells, which specialize in fighting both viral pathogens—think of the common cold—and altered cells of the organism itself, like cancerous tumor cells. Most of the time, the CD8 T-cells are “naïve”—mustered out of active duty and resting. But when they recognize foreign antigens after bumping into them, they suddenly wake up, turn into killer CD8 T-cells and attack whatever the pathogen may be, from the sniffles to cancer. After the killer T-cells have won their battle, most of them die.
“But,” says Leonid Pobezinsky, associate professor of veterinary and animal sciences at UMass Amherst and the paper’s senior author, “somehow a few CD8 T-cells survive, transform into memory cells and form an elite task force called the ‘memory pool’—they remember what that particular antigen looked like, so that they can be on the lookout for the next time it invades the body.”
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Microscopy images of antigen-inexperienced (‘naïve’) mouse CD8 T cells (green). A subset of these cells expresses Dapl1 protein (red), identifying a population committed to a memory stem-like lineage. Nuclei are shown in blue.
It is these CD8 memory T-cells that play critical roles in long-term immune protection and are central to tumor immunotherapies, because they are already primed to go into battle against specific pathogenic invaders. “They are fast to recognize a problem,” says Pobezinsky, “stronger to fight, and already know how to kill the specific threat. They don’t need to be trained.”
Immunological dogma has long held that naïve T-cells were “undecided,” meaning that it wasn’t until they were exposed to a pathogen that they began the process of transforming into the killer T-cells that would die or the ones that would wind up as memory cells, preserving the record of the invading pathogen for the future.
But what if this process could be sped up?
“What we found,” says Adam Lynch, a graduate student in Pobezinsky’s lab and the paper’s lead author, “runs counter to the long-held belief. There is a small population of naïve T-cells that always turn into memory cells. They are pre-wired to do so.”